Investigations of potential gene-environment interactions may improve our understanding of the etiology of breast cancer. The objectives of this proposal are to examine the association between DNA repair gene polymorphisms and breast cancer risk. In this proposal, we hypothesize that DNA repair pathways play an important role in protecting against breast carcinogenesis, and that polymorphisms in DNA repair genes, such as XPD, may influence breast cancer susceptibility in general, and possibly ionizing radiation-induced carcinogenesis, in particular. The applicant proposes to explore this hypothesis by designing and analyzing a nested ease-control study of the association between DNA repair gene polymorphisms and breast cancer incidence in a community-based cohort. Because of a complementary ongoing study, the applicant will also be able to compare the nested case-control results to a cohort analysis available for a subset of the population. The findings from this study will aid in understanding potential genetic susceptibility factors related to breast carcinogenesis, and in identifying women at increased breast cancer risk who may benefit from targeted interventions.